Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the acute renal failure that occurs after uranyl nitrate administration in the rat and the specific effects of pretreatment of rats with angiotensin converting enzyme inhibitor (CEI), plasma volume expansion (PVE) after uranyl nitrate, and a combination of these treatments. We utilized a combination of micropuncture measurements of glomerular hemodynamics, cage studies, and histologic examination of renal tissue to evaluate the degree of acute renal failure in all groups studied. Uranyl nitrate (UN) (25 mg/kg body wt) administration caused a reduction in the nephron filtration rate (SNGFR) (39.4 +/- 1.6 to 24.8 +/- 2.9 nl X min-1 X g kidney wt-1, P less than 0.02) as a result of a major decrease in the glomerular ultrafiltration coefficient (LpA) from control values (greater than or equal to 0.085 +/- 0.008 to 0.035 +/- 0.007 nl X sec-1 X mm Hg-1 X g kidney wt-1, P less than 0.01). Treatments with CEI, PVE, and the combination of CEI and PVE in rats receiving UN restored 0.38 +/- LpA to normal values (greater than 0.061 +/- 0.009, 0.091 +/- 0.020, and 0.138 +/- 0.020 nl X sec-1 X mm Hg-1 X g kidney wt-1, respectively). Cage studies revealed that CEI treatment prevented oliguria and resulted in major volume losses and reduction in weight. However, rats died after a similar period after UN, but probably by different mechanisms. Analysis of renal ultrastructure revealed equivalent tubular damage in all experimental groups. Alterations in LpA after UN are functional in nature and are potentially preventable and reversible by a combination of treatments with CEI and PVE.
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PMID:Functional basis for the glomerular alterations in uranyl nitrate acute renal failure. 300 41

The resident-intruder paradigm was employed in order to evoke an agonistic behavior in mice. In this situation a resident male mouse has been cohabiting with a female for 5 weeks, and an intruder male mouse is introduced into the resident's home cage. A species-specific pattern of agonistic behavior was observed in all mice. The significance of cholinergic mechanisms in the mediation of the agonistic behavior was evaluated by pharmacological manipulations. Drugs were administered to resident mice. Scopolamine hydrobromide (0.25, 0.50 and 0.75 mg/kg, i.p.) significantly suppressed the resident's aggressive episodes (offensive sideways posture, tail rattling and attack biting) in a dose-dependent manner, whereas the peripheral anticholinergic drug methylscopolamine nitrate (0.25, 0.50 and 0.75 mg/kg, i.p.) was ineffective. On the other hand, the resident's locomotor activity and rearing response were significantly increased after the administration of scopolamine hydrobromide. The evidence suggests that brain cholinoceptive mechanisms may participate in the regulation of intraspecies aggressive behavior. However, it appears that other nonspecific behavioral effects of scopolamine cannot be ruled out.
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PMID:Pharmaco-ethological analysis of agonistic behavior between resident and intruder mice: effect of anticholinergic drugs. 689 25

Gallium is a group IIIa transition metal that lowers serum calcium by an unknown mechanism and has been utilized in the treatment of cancer-associated hypercalcemia. The purpose of this study was to histomorphometrically investigate the ultrastructural effects of gallium nitrate on osteoclasts and osteoblasts in trabecular bone of normal nude mice and nude mice with humoral hypercalcemia of malignancy. Two groups of normal nude mice (n = 7 and n = 8, respectively) and two groups of hypercalcemic nude mice (n = 9) bearing a serially transplantable canine adenocarcinoma (CAC-8) were treated with vehicle or gallium nitrate. Osteoclasts were hypertrophied in vehicle-treated tumor-bearing nude mice as compared with vehicle-treated nontumor-bearing nude mice. Osteoclasts from tumor-bearing nude mice treated with gallium nitrate were significantly decreased in size and had fewer intracytoplasmic vesicles as compared with osteoclasts from vehicle-treated tumor-bearing nude mice. Degenerate osteoclasts, characterized by pyknotic nuclei and increased cytoplasmic vacuolation, were observed in both groups of gallium-treated nude mice. Osteoblasts from vehicle-treated tumor-bearing nude mice were hypertrophied and had extensive lamellar arrays of rough endoplasmic reticulum as compared with osteoblasts from vehicle-treated nontumor-bearing nude mice. Osteoblasts in gallium-treated nude mice (tumor-bearing and nontumor-bearing) were small and flattened with poorly developed cytoplasmic organelles. This investigation demonstrated that osteoclasts and osteoblasts in nude mice treated with gallium nitrate had ultrastructural evidence of decreased metabolic and functional activity. The results suggest that gallium nitrate lowers serum calcium by inhibiting osteoclastic bone resorption.
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PMID:Ultrastructural and histomorphometric evaluations of gallium nitrate on bone in nude mice bearing a canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy. 772 96

Nitric oxide and superoxide, which are produced by several cell types, rapidly combine to form peroxynitrite. This reaction can result in nitric oxide scavenging, and thus mitigation of the biological effects of superoxide. Also, superoxide can trap and hence modulate the effects of nitric oxide; superoxide dismutase, by controlling superoxide levels, therefore can influence the reaction pathways open to nitric oxide. The production of peroxynitrite, however, causes its own sequelae of events: Although neither .NO nor superoxide is a strong oxidant, peroxynitrite is a potent and versatile oxidant that can attack a wide range of biological targets. The peroxynitrite anion is relatively stable, but its acid, peroxynitrous acid (HOONO), rearranges to form nitrate with a half-life of approximately 1 s at pH 7, 37 degrees C. HOONO exists as a Boltzmann distribution of rotamers; at 5-37 degrees C HOONO has an apparent acidity constant, pKa,app, of 6.8. Oxidation reactions of HOONO can involve two-electron processes (such as an SN2 displacement) or a one-electron transfer (ET) reaction in which the substrate is oxidized by one electron and peroxynitrite is reduced. These oxidation reactions could involve one of two mechanisms. The first mechanism is homolysis of HOONO to give HO. and .NO2, which initially are held together in a solvent cage. This caged pair of radicals (the "geminate" pair) can either diffuse apart, giving free radicals that can perform oxidations, or react together either to form nitrate or to reform HOONO (a process called cage return). A large amount of cage return can explain the small entropy of activation (Arrhenius A-factor) observed for the decomposition of HOONO. A cage mechanism also can explain the residual yield of nitrate that appears to be formed even in the presence of high concentrations of all of the scavengers studied to date, since scavengers capture only free HO. and .NO2 and not caged radicals. If the cage mechanism is correct, the rate of disappearance of peroxynitrite be slower in solvents of higher viscosity, and we do not find this to be the case. The second mechanism is that an activated isomer of peroxynitrous acid, HOONO*, can be formed in a steady state. The HOONO* mechanism can explain the inability of hydroxyl radical scavengers to completely block either nitrate formation or the oxidation of substrates such as methionine, since HOONO* would be less reactive, and therefore more selective, than the hydroxyl radical itself.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. 776 72

Immunohistochemical and ultrastructural investigations of thyroid C cells were conducted in male nude (athymic) mice bearing a serially transplantable canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy following subcutaneous administration of gallium nitrate. The following four groups were investigated: 1) vehicle-treated non-tumor-bearing control mice; 2) non-tumor-bearing mice treated with gallium nitrate; 3) vehicle-treated hypercalcemic mice bearing CAC-8; and 4) CAC-8 tumor-bearing mice treated with gallium nitrate. Gallium nitrate-treated tumor-bearing mice had a significant decrease in serum calcium as compared with tumor-bearing controls. C cells of non-tumor-bearing mice stained intensely for calcitonin and calcitonin gene-related peptide and weakly for chromogranin A and neuron-specific enolase. In C cells of both vehicle- and gallium-treated tumor-bearing mice, immunoreactive staining was decreased for calcitonin, calcitonin gene-related peptide, and chromogranin A, whereas there was a moderate increase in staining for neuron-specific enolase. Ultrastructurally, thyroid C cells in hypercalcemic tumor-bearing control and gallium-treated mice were hypertrophic and markedly degranulated as compared with those of non-tumor-bearing controls. Hypertrophic C cells contained few mature secretory granules, a well-developed Golgi apparatus, and lamellar arrays of rough endoplasmic reticulum. There was no evidence of C-cell hyperplasia. Immunohistochemical and ultrastructural findings revealed that C cells in mice with cancer-associated hypercalcemia were primarily in the actively synthesizing phase of the secretory cycle and had diminished immunoreactivity for calcitonin, calcitonin gene-related peptide, and chromogranin A.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of humoral hypercalcemia of malignancy and gallium nitrate on thyroid C cells in nude mice: immunohistochemical and ultrastructural investigations. 805 30

To further understand the six-electron reductions of sulfite and nitrite catalyzed by the Escherichia coli sulfite reductase hemoprotein (SiRHP), we have determined crystallographic structures of the enzyme in complex with the inhibitors phosphate, carbon monoxide, and cyanide, the substrates sulfite and nitrite, the intermediate nitric oxide, the product sulfide (or, most likely, an oxidized derivative thereof), and an oxidized nitrogen species (probably nitrate). A hydrogen-bonded cage of ligand-binding arginine and lysine side chains, ordered water molecules, and siroheme carboxylates provides preferred locations for recognizing the common functional groups of these ligands and accommodates their varied sizes, shapes, and charged without requiring substantial structural changes. The coordination geometries presented here suggest that the successively deoxygenated sulfur and nitrogen species produced during catalysis need not alter their orientation in the active site to adopt new stable coordination states. Strong pi-acid ligands decrease the bond length between the siroheme and the proximal cysteine thiolate shared with the iron-sulfur cluster, emphasizing the ability of the coupled cofactors to promote electron tranfer into substrate. On binding the siroheme, the substrate sulfite provides an oxygen atom in a unique location of the binding site compared to all other ligands studied, induces a spin transition in the siroheme iron, flips an active-site arginine, and orders surrounding active-center loops. The loop that coalesces over the active center shields the positively charged ligand-coordinating residues from solvent, enhancing their ability to polarize the substrate. Hydrogen bonds supplied by active-site arginine and lysine residues facilitate charge transfer into the substrate from the electron-rich cofactors, activate S-O bonds for reductive cleavage, and provide potential proton sources for the formation of favorable aquo leaving groups on the substrate. Strong interactions between sulfite and ordered water molecules also implicate solvent as a source of protons for generating product water. From the structures reported here, we propose a series of key structural states of ligated SiRHP in the catalytic reduction of sulfite to sulfide.
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PMID:Probing the catalytic mechanism of sulfite reductase by X-ray crystallography: structures of the Escherichia coli hemoprotein in complex with substrates, inhibitors, intermediates, and products. 931 49

We have examined the reactions of peroxynitrite with short-chain aliphatic aldehydes to model the reaction of the peroxynitrite anion (ONOO-) with CO2. Aldehydes, like CO2, react rapidly with peroxynitrite and catalyze its decomposition. The pH dependence of the reaction is consistent with the addition of ONOO- (not ONOOH) to the carbonyl carbon atom of the free aldehyde forming a 1-hydroxyalkylperoxynitrite anion adduct (5), which structurally resembles the nitrosoperoxycarbonate adduct (1) formed from the reaction of ONOO- with CO2. Intermediate 5, or the secondary products derived from it, decays to give NO3- and regenerated aldehyde, with small but significant yields of H2O2, organic acids, and organic nitrates. In analogy with the peroxynitrite/CO2 system, it is suggested that 5 undergoes homolytic or heterolytic cleavage at the O-O bond, giving a caged radical pair [RCH(OH)O./ .NO2] (7) or intimate ion pair [RCH(OH)O -/+ NO2] (8). The radicals and ions in intermediates 7 and 8 can recombine within the solvent cage to form 1-hydroxyalkylnitrate [RCH(OH)ONO2] (6), which can then dissociate to give nitrate and regenerate the aldehyde. The aldehyde/ peroxynitrite adducts 5-8 mediate the oxidation of 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) but not the nitration of 4-hydroxyphenylacetate. The significance of these findings is discussed in relation to the mechanism(s) of the CO2-catalyzed isomerization of peroxynitrite to nitrate and biological nitrations involving peroxynitrite/CO2 adducts.
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PMID:Reactions of peroxynitrite with aldehydes as probes for the reactive intermediates responsible for biological nitration. 943 22

Nitric oxide (NO) is a powerful mediator with important actions in several organ systems. NO is synthesized during the enzymatic conversion of l-arginine and molecular oxygen to L-citrulline. About 90% of the NO formed is degraded to nitrate. Utilizing this information we have developed a method for assessment of the total rate of formation of NO in the rat. Male Wistar rats were kept in a closed-cage system allowing controlled breathing of a mixture of 18O2 and 16O2 in N2 for up to 5h. Blood samples for mass spectrometric analysis of nitrate residues with varying numbers of 18O atoms incorporated were drawn before and during the exposure to 18O2. By comparing the relative incorporation of 18O into nitrate residues to the 16O2/18O2 ratio in the breathing gas mixture in the cage system it was possible to calculate the absolute rate of NO formation in the animal. The rate of formation of NO in anaesthetized rats ranged from 0.33 to 0.85 micromol.kg-1.h-1. The rate of formation did not differ significantly in rats which were awake during the experiment (range 0.36-0.72 micromol.kg-1.h-1). The L-arginine analogue Nomega-nitro-L-arginine methyl ester (L-NAME) dose-dependently inhibited the formation of NO, at a dose of 100mg/kg by more than 99%. The technique presented allows estimation of the total rate of formation of NO in vivo in rats. Application of the technique may yield important information about the physiological and pathophysiological roles of NO. It may also be utilized to evaluate the effect of pharmacological treatment on NO formation.
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PMID:Estimation of total rate of formation of nitric oxide in the rat. 946 52

The effects of conditioned fear on gross activity, heart rate, PQ interval, noradrenaline and adrenaline were studied in freely moving rats. Subcutaneous (s.c.) injections of atropine methyl nitrate (0.5 mg/kg) during rest resulted in a significant shortening of the PQ interval, indicating that the PQ interval can be used as a measure of vagal activity. Conditioned fear was induced by 10-min forced exposure to a cage in which the rat had previously experienced footshocks (5 x 0.5 mA x 3 s). In non-shocked controls, an increase in gross activity was found and a pronounced tachycardia, without changes in PQ interval. Conditioned fear rats showed immobility behaviour, associated with a less pronounced tachycardia and an increase in PQ interval. Noradrenaline was similarly increased in both groups, whereas adrenaline was increased in conditioned fear rats only. To further evaluate the role of the vagus, rats were exposed to conditioned fear after pre-treatment with atropine methyl nitrate (0.5 mg/kg, s.c.). Again, immobility was observed with a concomitant tachycardia, but without an increase in PQ interval. These results indicate that the autonomic nervous system is differentially involved in heart rate regulation in conditioned fear rats and in non-shocked controls: in non-shocked controls a predominant sympathetic nervous system activation results in an increase in heart rate, whereas in conditioned fear rats the tachycardiac response is attenuated by a simultaneous activation of sympathetic nervous system and parasympathetic nervous system.
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PMID:Conditioned fear-induced tachycardia in the rat: vagal involvement. 969 10

The present study was designed to investigate whether antihypertensive and natriuretic effects of K were achieved by elevation of nitric oxide (NO) production in Dahl salt-sensitive (DS) rats. The rats were placed in individual metabolic cage and fed a high sodium diet with or without K supplementation for 4 weeks. K supplementation counteracted the blood-pressure raising effect of NaCl. K supplementation significantly enhanced sodium excretion and reduced sodium retention, increased the urinary nitrite plus nitrate excretion and kidney constitutive NO synthase activity in salt-loaded DS rats. These effect did not occur in the rats fed a low sodium diet with K supplementation. These results suggest that K supplementation attenuates development of hypertension with reduction of sodium retention in salt-loaded DS rats, which is mediated by the recovery of salt-induced NO production mechanism.
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PMID:Potassium supplementation increases sodium excretion and nitric oxide production in hypertensive Dahl rats. 1057 20


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